A Scaffolding Element Rewires Local 3D Chromatin Architecture During Differentiation
Upon differentiation chromatin rewires to reflect its new cellular identity and function. While it is widely known that this process involves cooperative changes in transcription, chromatin composition and 3D conformation, it is unclear what exactly drives these changes and how they influence one another. Here we used ESC-to-NPC differentiation to study rewiring at a 3 Mb large neuronal Zfp608 locus. During this process, this large chromatin domain splits in half right at the Zfp608 promoter, local chromatin gets littered with activating marks, compacts in 3D space and Zfp608 abounds in transcription. We investigated the cis and trans elements using capture Hi-C (cHi-C), extensive biophysical modelling, and 3-colour 3D-FISH with technical and analytical breakthroughs and found that transcription abundance modulates the contacts in the region as well as the insulation at the domain split. Furthermore, we found a genetic element we named scaffolding element, with a dual enhancer and arch